This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The goal of this project is to simulatneously measure the cerebral metabolic rate of oxygen (CMRO2) with MRI and diffuse optical spectroscopy (DOS). Multimodal MRI measurements will be made, including (1) local relative CMRO2 using a BOLD/ASL T[unreadable]2-weighted fast spin echo sequence calibrated using the inhalation of separate hyperoxic and hypercapnic epochs, (2) absolute whole brain CMRO2[unreadable] by measuring the phase and/or T2 and the velocity using phase contrast measurements of venous blood draining from the brain into the sagittal sinus, and (3) local absolute CMRO[unreadable]2 using inhaled oxygen-17 (17O) gas. DOS will be used to simultaneouly measure whole brain relaxtive CMRO2. Swine -- a large animal model with similar size and lung volume to that of humans -- will be used in lieu of human experiments for a two major reasons. First, 17O is not yet approved for human use. Second, we will produce a large increase in metabolism in the brain by using the metabolic poison 2,4-dinitrophenol (DNP), which cannot be used in humans. Our goal is to cross-validate the 17O and DOS measurements with more established methods of local and whole brain CMRO2 MRI measurement techniques, and determine whether the techniques produce different estimates and/or have sources of systematic bias.